Details of the Drug

General Information of Drug (ID: DMXA6B3)

• Drug Name: RO-4929097
• Synonyms: RO4929097; 847925-91-1; Ro 4929097; UNII-KK8645V7LE; KK8645V7LE; RG-4733; N1-[(7S)-6,7-dihydro-6-oxo-5H-dibenz[b,d]azepin-7-yl]-2,2-dimethyl-N3-(2,2,3,3,3-pentafluoropropyl)propanediamide; n1-((7s)-6,7-dihydro-6-oxo-5h-dibenz(b,d)azepin-7-yl)-2,2-dimethyl-n3-(2,2,3,3,3-pentafluoropropyl)propanediamide; OJPLJFIFUQPSJR-INIZCTEOSA-N; cc-19; MLS006011071; SCHEMBL1376366; GTPL7338; CHEBI:86474; DTXSID20233833; C22H20F5N3O3; MolPort-016-633-243; BCPP000088; EX-A1750; ZINC43208642; ABP000966; s1575; AKOS027250816

Indication

Disease Entry	ICD 11	Status	REF
Breast cancer	2C60-2C65	Phase 2	[1], [2]

• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 469.4
  Topological Polar Surface Area (xlogp); 4.6
  Rotatable Bond Count (rotbonds); 5
  Hydrogen Bond Donor Count (hbonddonor); 3
  Hydrogen Bond Acceptor Count (hbondacc); 8
• Chemical Identifiers:
  Formula: C22H20F5N3O3
  IUPAC Name: 2,2-dimethyl-N-[(7S)-6-oxo-5,7-dihydrobenzo[d][1]benzazepin-7-yl]-N'-(2,2,3,3,3-pentafluoropropyl)propanediamide
  Canonical SMILES: CC(C)(C(=O)NCC(C(F)(F)F)(F)F)C(=O)N[C@H]1C2=CC=CC=C2C3=CC=CC=C3NC1=O
  InChI: InChI=1S/C22H20F5N3O3/c1-20(2,18(32)28-11-21(23,24)22(25,26)27)19(33)30-16-14-9-4-3-7-12(14)13-8-5-6-10-15(13)29-17(16)31/h3-10,16H,11H2,1-2H3,(H,28,32)(H,29,31)(H,30,33)/t16-/m0/s1
  InChIKey: OJPLJFIFUQPSJR-INIZCTEOSA-N
• Cross-matching ID:
  PubChem CID: 49867930
  ChEBI ID: CHEBI:86474
  CAS Number: 847925-91-1
  DrugBank ID: DB11870
  TTD ID: D0I3WC

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Gamma-secretase (GS)	TT9W8GU	APH1A_HUMAN; APH1B_HUMAN; PEN2_HUMAN; NICA_HUMAN; PSN1_HUMAN	Modulator	[2], [3]

Molecular Expression Atlas of This Drug

• The Studied Disease: Breast cancer
• ICD Disease Classification: 2C60-2C65

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Gamma-secretase (GS)	DTT	APH1A; APH1B; NCSTN; PSENEN; PSEN1	1.47E-02	-0.09	-0.37

References

• [1] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7338).
• [2] Phase I study of RO4929097, a gamma secretase inhibitor of Notch signaling, in patients with refractory metastatic or locally advanced solid tumors. J Clin Oncol. 2012 Jul 1;30(19):2348-53.
• [3] Phase 2 study of RO4929097, a gamma-secretase inhibitor, in metastatic melanoma: SWOG 0933.Cancer.2015 Feb 1;121(3):432-440.
• [4] The geminal dimethyl analogue of Flurbiprofen as a novel Abeta42 inhibitor and potential Alzheimer's disease modifying agent. Bioorg Med Chem Lett. 2006 Apr 15;16(8):2219-23.
• [5] Clinical pipeline report, company report or official report of Roche (2009).
• [6] A phase 3 trial of semagacestat for treatment of Alzheimer's disease. N Engl J Med. 2013 Jul 25;369(4):341-50.
• [7] Pharmacodynamics and pharmacokinetics of the gamma-secretase inhibitor PF-3084014.J Pharmacol Exp Ther.2010 Jul;334(1):269-77.
• [8] Determination of the gamma-secretase inhibitor MK-0752 in human plasma by online extraction and electrospray tandem mass spectrometry (HTLC-ESI-MS/MS). J Chromatogr B Analyt Technol Biomed Life Sci. 2010 Sep 1;878(25):2348-52.
• [9] Safety and tolerability of the gamma-secretase inhibitor avagacestat in a phase 2 study of mild to moderate Alzheimer disease. Arch Neurol. 2012 Nov;69(11):1430-40.
• [10] CHF5074, a novel gamma-secretase modulator, attenuates brain beta-amyloid pathology and learning deficit in a mouse model of Alzheimer's disease.Br J Pharmacol.2009 Mar;156(6):982-93.
• [11] Clinical pipeline report, company report or official report of Ayala Pharmaceuticals.
• [12] Modulation of gamma-secretase for the treatment of Alzheimer's disease. Int J Alzheimers Dis. 2012;2012:210756.